Human anti-ANTXR chimeric antigen receptor and use thereof

Abstract

The present invention relates to a chimeric antigen receptor having a ligand specifically targeting an anthrax toxin receptor (ANTXR), and, more specifically, to: a nucleic acid encoding a chimeric antigen receptor comprising ligand PA63 specifically binding to anthrax toxin receptor 1 (ANTXR1) or anthrax toxin receptor 2 (ANTXR2); a vector comprising the nucleic acid encoding a chimeric antigen receptor; and a recombinant cell comprising the vector; a pharmaceutical composition for preventing or treating solid cancer, comprising the recombinant cell; and a treatment method. Solid cancer can be treated using an anti-ANTXR chimeric antigen receptor (CAR)-T cell, according to the present invention, and since the chimeric antigen receptor (CAR)-T cell is administered to patients with solid cancer for whom anti-cancer drug administration is not effective, especially patients with pancreatic cancer, drug administration is limited, and customized solid cancer prevention or treatment, which are efficient and safe, is possible.

What is claimed is: 
     
       1. A nucleic acid encoding a chimeric antigen receptor (CAR) comprising an extracellular binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the extracellular binding domain is domain 4 (D4) of a PA63 ligand or a fragment comprising domain 4 (D4) and domain 3 (D3) of a PA63 ligand, and recognizes an anthrax toxin receptor (ANTXR). 
     
     
       2. The nucleic acid according to  claim 1 , wherein the PA63 ligand comprises the amino acid sequence of SEQ ID NO:1. 
     
     
       3. The nucleic acid according to  claim 1 , wherein the domain 4 of the PA63 ligand comprises the amino acid sequence of SEQ ID NO:2. 
     
     
       4. The nucleic acid according to  claim 1 , wherein the fragment comprising domain 4 of the PA63 ligand comprises the amino acid sequence of SEQ ID NO: 5. 
     
     
       5. The nucleic acid according to  claim 1 , wherein the ANTXR is ARTXR1 (anthrax toxin receptor 1) or ARTXR2 (anthrax toxin receptor 2). 
     
     
       6. The nucleic acid according to  claim 1 , wherein the transmembrane domain is selected from the group consisting of an alpha, beta or zeta chain of a T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, and CD154. 
     
     
       7. The nucleic acid according to  claim 1 , wherein the intracellular signaling domain comprises a primary signaling domain and a co-stimulatory signaling domain. 
     
     
       8. The nucleic acid according to  claim 7 , wherein the primary signaling domain is selected from the group consisting of TCRζ, FcRγ, FcRβ, CD3γ, CD3δ, CD3ε, CD3ζ, CD22, CD79a, CD79b, and CD66d. 
     
     
       9. The nucleic acid according to  claim 7 , wherein the co-stimulatory signaling domain is selected from the group consisting of OX40, CD2, CD27, CD28, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), and 4-1BB (CD137). 
     
     
       10. A vector comprising the nucleic acid encoding the chimeric antigen receptor according to  claim 1 . 
     
     
       11. The vector according to  claim 10 , wherein the vector is selected from the group consisting of DNA, RNA, plasmids, lentiviral vectors, adenovirus vectors, and retroviral vectors. 
     
     
       12. A recombinant cell comprising the vector according to  claim 10 . 
     
     
       13. The recombinant cell according to  claim 12 , wherein the cell is a T cell or NK cell. 
     
     
       14. The recombinant cell according to  claim 13 , wherein the T cell is selected from the group consisting of cytotoxic T lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), and T cells isolated from peripheral blood mononuclear cells (PBMCs). 
     
     
       15. A method of inhibiting or delaying the progression of a solid cancer expressing an ANTXR (anthrax toxin receptor) or alleviating or eliminating symptoms of such solid cancer in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising the recombinant cell according to  claim 12 . 
     
     
       16. The method according to  claim 15 , wherein the solid cancer is selected from the group consisting of pancreatic cancer, gastric cancer, colon cancer, lung cancer, breast cancer, germ cell cancer, liver cancer, skin cancer, bladder cancer, prostate cancer, uterine cancer, cervical cancer, and ovarian cancer.